Duchenne Muscular Dystrophy
Conditions
Keywords
Recombinant fusion protein, Muscle-wasting disease, Ambulatory function, Pharmacokinetics, Pharmacodynamics
Brief summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of KER-065 administered to adult and pediatric ambulatory and nonambulatory male participants with Duchenne Muscular Dystrophy (DMD) on stable background therapy.
Detailed description
This is a Phase 2, multicenter, open-label study of KER-065. The study will consist of 3 periods: * Screening Period (up to 6 weeks) * Treatment Period (48 weeks) * Safety Follow-up Period (4 weeks) Participants will be enrolled in parallel into 1 of 3 treatment cohorts: * Cohort A1 (Late Ambulatory) * Cohort A2 (Late Ambulatory) * Cohort N1 (Early Nonambulatory)
Interventions
DRUGKER-065
KER-065 will be administered subcutaneously (SC)
Sponsors
Keros Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
9 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Diagnosis of DMD, defined as the presence of phenotypic features at screening consistent with DMD AND documented mutation in the dystrophin gene consistent with the diagnosis of DMD using a clinically validated genetic test. * Receiving a stable regimen of systemic CS (including, but not limited to, prednisone, prednisolone, deflazacort, or vamorolone) for at least 90 days before screening. * Body weight of ≥ 25.0 kg. Ambulatory Participants Only (Cohort A1 and A2): * Ambulatory, defined as able to walk independently without assistive devices. * Able to TTR in \< 10 seconds. * Has a NSAA score ≥ 15 points. * Cohort 2 only: Documentation of a stable dose of an approved exon-skipping therapy. Nonambulatory Participants Only (Cohort N1): * Nonambulatory, characterized as being unable to ambulate for a minimum of 3 months before first dose with onset of nonambulatory status AND a NSAA walk score of 0 and inability to perform the 10MWR. * PUL v2.0 entry item score of 3 to 5, inclusive. Key
Exclusion criteria
* Clinical symptoms or signs of cardiomyopathy or heart failure. * Exposure to any approved or investigational dystrophin restoration gene therapy product. * Exposure to any approved or investigational dystrophin restoration product other than gene therapy (Except for exon-skipping therapy for Cohort A2). * Exposure to any approved or investigational histone deacetylase inhibitor, antimyostatin therapy, therapy targeting transforming growth factor-beta ligands, or cell-based therapy. * Use of any other pharmacological treatment, except for CS * Treatment with immunosuppressant therapy (other than CS) * History of fracture of the upper limb Nonambulatory Participants Only (Cohort N1): * Elbow-flexion contractures \> 30° in both upper extremities. * Forced vital capacity (FVC) of \< 50% or requirement for daytime or nocturnal ventilation, except for nocturnal non-invasive ventilation AND inability to perform consistent FVC measurements within ± 15% during paired testing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-emergent adverse events (TEAEs and serious adverse events (SAEs) | Up to approximately 14 months | To evaluate the safety and tolerability of KER-065 in ambulatory and nonambulatory participants with DMD |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| KER-065 serum concentration by visit, as appropriate | Up to Week 52 | To assess the pharmacokinetics (PK) of KER-065 in ambulatory and nonambulatory participants with DMD |
| Number and proportion of participants with treatment-emergent ADA (antidrug antibody) by visit | Up to Week 52 | To assess the immunogenicity of KER-065 in ambulatory and nonambulatory participants with DMD |
| Change from baseline by visit in bone mineral density (BMD), fat mass, and lean body mass, as measured by dual- energy X-ray absorptiometry (DXA) | Week 12, Week 24 and Week 48 | To assess the effect of KER-065 on body composition in ambulatory and nonambulatory participants with DMD |
| Change from baseline by visit in muscle volume and intramuscular fat by skeletal muscle Magnetic Resonance Imaging (MRI) | Week 24 and Week 48 | To assess the effect of KER-065 on skeletal muscle in ambulatory and nonambulatory participants with DMD |
| Ambulatory: Change from baseline by visit in North Star Ambulatory Assessment (NSAA) total score | Week 24 and Week 48 | To assess the effect of KER-065 on motor function in ambulatory participants with DMD |
| Ambulatory: Change from baseline by visit in 4-stair climb (4SC) | Week 24 and Week 48 | To assess the effect of KER-065 on motor function in ambulatory participants with DMD |
| Ambulatory: Change from baseline by visit in 10-meter walk/run (10MWR) test | Week 24 and Week 48 | To assess the effect of KER-065 on motor function in ambulatory participants with DMD |
| Ambulatory: Change from baseline by visit in time to rise (TTR) | Week 24 and Week 48 | To assess the effect of KER-065 on motor function in ambulatory participants with DMD |
| Nonambulatory: Change from baseline by visit in Performance of Upper Limb (PUL) v2.0 score | Week 24 and Week 48 | To assess the effect of KER-065 on motor function in nonambulatory participants with DMD |
Contacts
CONTACTGina Weaver
Outcome results
None listed